Contribution of Distinct Homeodomain DNA Binding Specificities to Drosophila Embryonic Mesodermal Cell-Specific Gene Expression Programs
| Autor: | Stephen S. Gisselbrecht, Leila Shokri, Terese Tansey, Brian W. Busser, Caitlin E. Gamble, Martha L. Bulyk, Alan M. Michelson |
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| Přispěvatelé: | Harvard University--MIT Division of Health Sciences and Technology, Bulyk, Martha L. |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Embryo
Nonmammalian Gene regulatory network lcsh:Medicine Genes Insect Biology Cell fate determination Mesoderm 03 medical and health sciences 0302 clinical medicine Animals Drosophila Proteins Hox gene Enhancer lcsh:Science Transcription factor 030304 developmental biology Regulation of gene expression Genetics Homeodomain Proteins 0303 health sciences Multidisciplinary Binding Sites Base Sequence Pioneer factor lcsh:R Gene Expression Regulation Developmental DNA 3. Good health Cell biology Drosophila melanogaster Enhancer Elements Genetic Mutagenesis Organ Specificity embryonic structures Homeobox lcsh:Q 030217 neurology & neurosurgery Protein Binding Transcription Factors Research Article |
| Zdroj: | PLoS PLoS ONE PLoS ONE, Vol 8, Iss 7, p e69385 (2013) |
| Popis: | Homeodomain (HD) proteins are a large family of evolutionarily conserved transcription factors (TFs) having diverse developmental functions, often acting within the same cell types, yet many members of this family paradoxically recognize similar DNA sequences. Thus, with multiple family members having the potential to recognize the same DNA sequences in cis-regulatory elements, it is difficult to ascertain the role of an individual HD or a subclass of HDs in mediating a particular developmental function. To investigate this problem, we focused our studies on the Drosophila embryonic mesoderm where HD TFs are required to establish not only segmental identities (such as the Hox TFs), but also tissue and cell fate specification and differentiation (such as the NK-2 HDs, Six HDs and identity HDs (I-HDs)). Here we utilized the complete spectrum of DNA binding specificities determined by protein binding microarrays (PBMs) for a diverse collection of HDs to modify the nucleotide sequences of numerous mesodermal enhancers to be recognized by either no or a single subclass of HDs, and subsequently assayed the consequences of these changes on enhancer function in transgenic reporter assays. These studies show that individual mesodermal enhancers receive separate transcriptional input from both I–HD and Hox subclasses of HDs. In addition, we demonstrate that enhancers regulating upstream components of the mesodermal regulatory network are targeted by the Six class of HDs. Finally, we establish the necessity of NK-2 HD binding sequences to activate gene expression in multiple mesodermal tissues, supporting a potential role for the NK-2 HD TF Tinman (Tin) as a pioneer factor that cooperates with other factors to regulate cell-specific gene expression programs. Collectively, these results underscore the critical role played by HDs of multiple subclasses in inducing the unique genetic programs of individual mesodermal cells, and in coordinating the gene regulatory networks directing mesoderm development. National Institutes of Health (U.S.) (Grant R01 HG005287) |
| Databáze: | OpenAIRE |
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